Innovating Shorter, All- Oral, Precised, Individualized Treatment Regimen for Rifampicin Resistant Tuberculosis：Contezolid, Delamanid and Bedaquiline Cohort (INSPIRE-CODA)

Beijing Chest Hospital

Status and phase: Active, not recruiting; Phase 3

Conditions: Rifampicin-resistant Tuberculosis; Pulmonary Tuberculosis

Treatments: Drug: Contezolid; Drug: Pyrazinamide; Drug: Linezolid; Drug: Cycloserine; Drug: Ethambutol; Drug: Moxifloxacin; Drug: Clofazimine; Drug: Levofloxacin; Drug: Para-Aminosalicylic Acid; Drug: Prothionamide; Drug: Delamanid; Drug: Bedaquiline

Study type: Interventional

Funder types: Other

Identifiers

NCT06081361

BJCH-202301

Details and patient eligibility

About

The goal of this clinical trial is to compare the efficacy and safety of a Contezolid and Delamanid-Containing short regimen to standard longer regimen in Rifampicin-resistant pulmonary tuberculosis (RR-TB). The main questions it aims to answer are:

• Is the efficacy of short regimen non-inferior to standard regimen?
• Is the short regimen safe enough to replace the standard regimen?

Participants will:

• Be given with either short or standard regimen for RR-TB treatment
• Be asked to complete the scheduled visit as planned.

Enrollment: 186 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥18y and <70y when signing informed consent;
2. Initial or re-treatment for pulmonary tuberculosis with:

1. MTB positive in sputum or bronchoalveolar lavage fluid culture at or within 3 months before screening, or MTB positive in molecular test at or within 3 months before screening, and; 2) recorded Rifampicin-resistance at or before screening; 3. Imaging (Chest X-ray or CT scan) proved pulmonary tuberculosis within 1 year before screening; 4. Never used BDQ, DLM or CZD, or the accumulative duration of any of the treatment is not more than 2 weeks 5. For women in childbearing age, negative in pregnancy test and effective contraceptive measures throughout study is required; 6. For men, effective contraceptive measures is required; 7. Willing to participate the study and sign informed consent.

Exclusion criteria

1. The participant will be excluded by investigator based on the medical history or concomitant diseases such as serious metabolic disease, cardiovascular disease, hepatobiliary disease, renal disease, autoimmune disease, neuropsychiatric disorders, hematological disease, malignant neoplastic disease and so on; or the study will have negative impact on the well-being of the participant, or the participant is considered unable to complete the evaluation by investigator;
2. History of alcohol or drug abuse that the study is considered have negative impact on the well-being of the participant by investigator;
3. HIV positive;
4. Chronic hepatitis with HBsAg, HBeAg and anti-HBC antibody positive, or HBV-DNA>1000 CPs/mL with rising ALT/AST;
5. Allergic to or known hypersensitive to any of study drugs;
6. Extensive (or advanced) pulmonary TB disease: presence of bilateral cavitary disease or extensive parenchymal damage on chest radiography;
7. Hematogenous disseminated pulmonary tuberculosis and serious extrapulmonary tuberculosis (such as tuberculosis in digestive system, urogenital system, osteoarticular tuberculosis, tuberculous meningitis);
8. With any of following risk factors for cardiovascular disease: 1) history of arrhythmia and on consequential treatment; 2) QTcF>500ms on ECG; 3) history of ventricular arrhythmia; 4) torsade de pointe with heart failure, hypokalemia or familial long Q-T syndrome; 5) other possible risk factor for arrythmia;
9. Previous or current optic nerve disorder that may progress or deteriorate during the study by investigator's consideration;
10. Was enrolled within 2 months before screening, or currently in other studies; except for those who participating observational study or in the post-treatment period;
11. Being considered unlikely to survive for more than 6 months by investigator;
12. BMI < 17kg/m2
13. May need surgical procedures based on the evaluation of pulmonary lesions;
14. May continuous use prohibited concomitant medications that is considered not suitable for the study by investigator;
15. Positive in pregnancy test or known pregnancy, breastfeeding, or plan to become pregnant during or within 6 months after the study treatment;
16. Abnormal laboratory test results: 1) Plasma potassium lower than lower limit of normal (LLN); 2) Hb < 8.0 g/dL； 3) platelet count <75,000/mm3； 4) WBC count<3000/mm3； 5）AST/ALT >3×ULN； 6）creatinine>2×ULN；7）total bilirubin>2×ULN, or >1.5×ULN，with abnormal AST or ALT; 8) Albumin < 30g/L

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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186 participants in 2 patient groups

Short-Term Regimen

Experimental group

Description:

Intervention will be determined based on Fluoroquinolones(FQs) resistance. * For those sensitive to FQs: BDQ DLM CZD LFX(MFX) for 6 months * For those resistant to FQs: BDQ DLM CZD CFZ for 6 months

Treatment:

Drug: Levofloxacin

Drug: Clofazimine

Drug: Bedaquiline

Drug: Moxifloxacin

Drug: Delamanid

Drug: Contezolid

Standard Regimen

Active Comparator group

Description:

Intervention will be determined based on Fluoroquinolones(FQs) resistance. * For those sensitive to FQs: BDQ LZD LFX(MFX) CS CFZ regimen for 6 months, then LFX(MFX) CS CFZ for 12 months * For those resistant to FQs: LFX(MFX) will be replaced by Pto, PZA, PAS or EMB

Treatment:

Drug: Levofloxacin

Drug: Clofazimine

Drug: Bedaquiline

Drug: Moxifloxacin

Drug: Ethambutol

Drug: Prothionamide

Drug: Cycloserine

Drug: Linezolid

Drug: Pyrazinamide

Drug: Para-Aminosalicylic Acid